Several laboratories, including our own, have presented data linking
the pathogenesis of MS to active HHV-6 infections. Blood samples were obtained
at the time of new clinical relapse in patients with relapsing-remitting
MS and assessed for active HHV-6 infection by plasma PCR. Then, several
weeks later (mean interval:68 days), a second blood sample was obtained
from the same patients and assessed for active HHV-6 infection. Patients'
changes of Expanded Disability Status Scale (EDSS) from the relapse and
treatments at the time samples were obtained were noted. Five of
39 (13%) patients had at least one sample positive for active HHV-6 infection.
Variant typing of the positive samples was possible with 3 of the 5 positives,
and 2 were HHV-6 variant A. Four of the five (80%) positive samples
were obtained at the time of relapse whereas only one (20%) positive was
observed in a patient after relapse. The HHV-6 positive patients
suffered a larger change in their EDSS (mean EDSS change of 1.4) than the
HHV-6 negative patients (mean EDSS change of 0.7). It was also found that
the patients receiving either beta interferon or glatirimar acetate (copaxone)
were less likely to be HHV-6 positive (2/30; 7%) than the patients receiving
no treatment 3/9; 33%). Since the majority (>75%) of the patients
on therapy were receiving beta interferon, the decreased positivity
for active HHV-6 may reflect the known antiviral properties of beta interferon.

Introduction

In a recently published study, Knox et al. (Clin Infect Dis 2000; 31:894-903)
identified, by means of a rapid culture assay, active HHV-6 viremia in
54% (22/41) of patients with MS. HHV-6 viremia was not detected in
61 healthy controls.

Based on these findings and the tropism of HHV-6 for blood leukocytes,
the possibility was raised that the CNS lesions of MS are the result of
invasion of the CNS by HHV-6 from the peripheral blood.

Patients And Methods

Patients and Controls

Thirty-nine patients, with relapsing remitting MS had blood samples drawn
at the time of a clinical relapse.

No patients were receiving corticosteroids when the specimens were drawn.
Most patients received corticosteroid treatment after onset of their disease
relapse.

A second blood specimen was drawn from 36 of the same patients six
to ten weeks later after the relapse had resolved.

Any treatment that the patients were receiving at the time of the first
blood specimen was noted. Also, the changes in the patients' Expanded
Disability Status Scale (EDSS) score due to the disease relapse were determined.

46 control plasma specimens were obtained from six healthy donors over
a mean period of 140 days (range 62 days to 183 days).

DNA PCR was performed using a hotstart taq DNA polymerase system [TaqBead
Hot Start Polymerase; Promega Corp.; Madison, Wisconsin]. The HHV-6 specific
primer pair used has been described in detail previously (Drobyski et al;
NEJM 1994; 330:1356-1360). This PCR system can detect approximately
200 viral genomes per ml of plasma (5 genomes per PCR reaction).
Quantitation of the PCR reaction was accomplished by amplification of a
quantitative DNA target control. The HHV-6 variant involved in the
positive samples was determined by means of variant specific restriction
enzymes.

Results

Incidence of Active HHV-6 Infections in MS Patients at Time of Relapse
Compared with Healthy Control Individuals.